Neuroscience Drosophila Facility

Drosophila locomotion tracking in real time

We use Any-maze (https://www.any-maze.com/), an extremely powerful animal tracking software package, developed for vertebrate models but we have optimised it for live real-time tracking of Drosophila locomotion. Up to 40 individual flies can be tracked simultaneously in real time. Quantitative analysis of average speed, total distance, positional information and many other parameters can be analysed. Bespoke tracking and analysis programs can be easily developed using the intuitive interface.

Drosophila circadian rythym and sleep analysis

We utilise TriKinetics activity monitors (https://www.trikinetics.com/), which are the most frequently used system for tracking circadian rhythm and sleep in Drosophila. The DAM5H Drosophila Activity Monitor measures the locomotor activity of 32 individual flies using 15 infrared beams per tube. We use the DAM5H for long term monitoring of Drosophila locomotion, circadian rhythm and sleep.

Appetite and feeding behaviour

We use the CApillary FEeder Assay (https://pubmed.ncbi.nlm.nih.gov/28362419/) to measure food intake in Drosophila. Feeding and appetite can be disrupted in a range of neurological and psychiatric disorders.

Detection of painful stimuli (nociception) using the Jump assay

Assessment of Drosophila jumping behaviour upon exposure to rising temperatures is a robust measure of injury-induced hypersensitivity to heat [https://en.bio-protocol.org/e4079]. Our automated system provides a medium through-put capability set up and enables a daily analysis of up to 300 individual flies to study conserved mechanisms important for acute and chronic pain.

1D analysis of motor activity – vibrating platform

The Drosophila arousal tracking system (DART) software (Faville, R. et al. Sci Rep 5, 8454 (2015)) is used to track and quantify fly motor behaviour elicited by a train of vibration stimuli or endogenously generated (Mazaud, D. et al. J Neurosci 39, 5269-5283 (2019)) on a motor-controlled platform with IR illumination developed by BFK Lab Ltd (http://www.bfklab.com/).

1D analysis of seizures – thermal platform

We are adapting the Drosophila arousal tracking system (DART) software (Faville, R. et al. Sci Rep 5, 8454 (2015))  to track and quantify seizures in flies, elicited by hyperthermia. A novel hydrodynamic platform is being manufactured by BFK Lab Ltd (http://www.bfklab.com/) and we have run a proof of concept analysis with DART. We aim to having this platform operative in 2022.

1D analysis of motor activity – RGB stimulation

The Drosophila arousal tracking system (DART) software (https://pubmed.ncbi.nlm.nih.gov/25677943/) is used to track and quantify fly motor behaviour in an optogenetic enclosure.

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Development of neural circuitry (Tear)​

During development, growing axons are guided to their appropriate targets by extracellular cues, the response to which depends crucially on the repertoire of receptors expressed by each axon and the intracellular mechanisms that transduce and regulate the response to these cues. In the past this research area has been significantly advanced by the identification of several major families of guidance cues and their cognate receptors and the elucidation of many aspects of the molecular mechanisms of axon guidance. However, globally we still have only a rudimentary understanding of how these axon guidance processes are coordinated to specify the precise wiring of billions of cells in thousands of tracts in the brain. ​

To fully understand this process it will be necessary to identify additional genes involved in wiring, define their expression patterns over the course of development and elucidate their cellular functions and molecular interactions. Through genetic and bioinformatic approaches we have identified further molecules that regulate the development of connectivity in the embryonic central nervous system (CNS) of Drosophila. Currently we are focusing our investigations on additional genes that contribute to guiding axons towards the midline of the CNS.

mTOR signalling in neurodevelopmental disease (Bateman)

mTOR, or mechanistic target of rapamycin, is a large protein kinase and a crucial sensor of cellular anabolic processes. mTOR signalling regulates a wide variety of cellular functions, including growth control, mitochondrial function, autophagy and lipid synthesis. Activation of mTOR signalling also causes neurological diseases associated with epilepsy, autism spectrum disorders and intellectual disability.

We are interested in understanding the role of mTOR in nervous system development and how activation of mTOR signalling causes neurological disease. We use Drosophila to identify new components of the mTOR pathway and understand their function in Drosophila nervous system development. In the long term, understanding how mTOR contributes to neurological disease will lead to new treatments for these devastating diseases.

Autophagy in the nervous system in health and disease (Fanto)

Autophagy is a fundamental housekeeping mechanism for long lived cells like neurons. Its efficiency decades with age and can become dysfunctional either because of genetic mutations (primary autophagy defects) or because of excessive accumulation of misfolded proteins or damaged organelles (secondary autophagy defects). Using Drosophila, we study how autophagy impacts neuronal structure and function.   

Mitochondrial disease (Bateman)

Primary mitochondrial diseases are caused by mutations in genes that affect mitochondrial function. Patients have a range of symptoms affecting the nervous system and muscle. We use genetic tools to generate flies with nervous system specific mitochondrial dysfunction. Using these Drosophila models we have provided important insight into the mechanisms underlying mitochondrial disease.

Intracellular trafficking, ageing and neurodegeneration (Vagnoni)

We are studying the cell biology of the neuron with a focus on the relationship between intracellular trafficking and neuronal function. The lab is particularly interested in studying the transport of organelles and vesicles in the axons of neurons during ageing and neurodegeneration. We routinely use live cell imaging, super resolution and light sheet microscopy of adult neurons. Expanding the available toolkit to study cytoskeletal trafficking is also an important part of our work and we are happy to share our knowledge and our reagents as they become available.

http://www.vagnonilab.com/ 

Nociception & Pain mechanisms (Baron) 

Nociception as a mechanism of sensing noxious stimuli and escaping potential harm is widely conserved across metazoan species, including the fruit fly. We use the adult Drosophila to study molecular mechanisms that are activated in peripheral somatosensory neurons (nociceptors) upon injury – mimicking nociceptive sensitisation similar to that observed in human chronic pain conditions. Identification of molecular mechanisms (molecular markers) involved in nociceptive sensitisation facilitates the use of genetic biosensor tools for further mechanistic and pharmacological studies.

Drosophila as a model for neurodegenerative disease (Tear)

The Tear group are using Drosophila to increase our understanding of gene products associated with Alzheimer’s and Batten disease. We use humanised Drosophila that express human tau and specific identified human kinases to create an AD-like pathology. We are beginning to discriminate the specific involvement of the different kinases alone or together in the creation of toxic forms of tau. Batten disease, also known as neuronal ceroid lipofuscinoses (NCLs), describes a group of at least nine fatal monogenetic neurodegenerative disorders that primarily affect infants and children. The genes mutated in several forms of the disorder have been identified recently, but very little is known about the precise roles of these gene products. We investigate the role of the transmembrane proteins Cln7 and Cln3, which are affected in the most common forms of NCL. Drosophila Cln3 shares many properties with the vertebrate form, it is localised to the endosomal-lysosomal compartment in many cell type and found at the synapse. We are investigating the roles these proteins play in the normal function and development of the neuromuscular junction.

Who we are

• Professor Joseph Bateman, Basic and Clinical Neuroscience (KCL NDF coordinator, contact for general enquiries about the KCL NDF)​
• Dr Frank Hirth, Basic and Clinical Neuroscience ​
• Dr Manolis Fanto, Basic and Clinical Neuroscience ​
• Dr Alessio Vagnoni, Basic and Clinical Neuroscience ​
• Jemeen Sreedharan, Basic and Clinical Neuroscience​
• Professor Guy Tear, Department of Developmental Neurobiology​
• Dr Darren Williams, Department of Developmental Neurobiology​
• Dr Rita Sousa-Nunes, Department of Developmental Neurobiology​
• Dr Olga Baron, Wolfson Centre for Age-Related Disease 

Accessing the KCL NDF

• Collaborate with us to use our developmental, evolutionary, ageing and neurodegenerative disease models.
• Get training from us. We can train students and postdocs in our tools, techniques and platforms to add new dimensions to your research.
• We can provide advice and support. Contact us with any questions about our works, models and platforms.
• For enquires about the KCL NDF contact the coordinator Joseph Bateman or relevant lab heads.

To contact us or find out more about our research click on the profiles below